[2092] Complete data from the letrozole (L), exemestane (E), and anastrozole (A) pharmacodynamic (PD) 
LEAP trial: direct comparison of safety parameters between aromatase inhibitors (AIs) in healthy postmenopausal women.
McCloskey E, Hannon R, Lakner G, Clack G, Miyamoto A, Finkelman R, Eastell R.. University of Sheffield, Sheffield, United Kingdom; MAV Hospital, Budapest, Hungary; AstraZeneca, Macclesfield, Cheshire, United Kingdom; AstraZeneca, Wilmington, DE
Background: LEAP was an open, randomized Phase I study, comparing the effects of A, L, and E on bone formation and resorption markers, lipid profiles, adrenal function and adverse events in healthy volunteers, to identify potential differences in their safety profiles. Methods: Subjects received oral A (1mg), L (2.5mg), or E (25mg) od for 24 weeks (w) with PD variables assessed at baseline, 12w, 24w, and 36w (12w post-dosing). Changes from baseline in fasting serum lipid variables at 12 and 24w and changes in log-transformed bone marker levels at 24w on A were compared with those on L and E by ANCOVA with no multiple comparison adjustment. Results: 90 volunteers were evaluable. There were no significant differences in lipid profiles for either L or E compared with A, except for a higher increase in triglycerides with L than A (+9.6% and -2.9%, respectively, at 12w; p<0.05) and a more marked reduction in high-density lipoprotein cholesterol with E than A (-13.9% and 0.3%, respectively, at 24w; p<0.001). The ratio of high- to low-density lipoprotein cholesterol for E was significantly higher than with A (17.09% and 4.6%, respectively, at 24w; p<0.05 at 24w). There were no formal comparisons at 36w. Percent changes in bone marker levels from baseline, with 95% confidence intervals, at 24w for women receiving A, L, and E, are shown below.
bALP, bone alkaline phosphatase; PINP propeptide of type-I collagen; CTX, serum C-telopeptide crosslinks; PTH, parathyroid hormone; *p=0.04 vs A
The only significant difference between the AIs was a greater PTH decrease for E vs A (p=0.04). At 36w changes in bone turnover markers persisted, with high inter-subject variability, but PTH levels returned to baseline. Discussion: These data support those from non-comparative studies showing different serum lipid effects for A, L, and E. Each AI increased bone turnover.
| Marker | A (n=29) | L (n=29) | E (n=32) |
| bALP (formation) | +2 (-4, 9) | +3 (-3, 9) | +7 (1, 13) |
| PINP (formation) | +14 (3, 25) | +11 (2, 22) | +23 (13, 35) |
| CTX (resorption) | +16 (3, 32) | +28 (14, 43) | +23 (10, 37) |
| PTH | -8 (-18, 4) | -11 (-20, 0) | -21* (-28, -12) |
| bALP, bone alkaline phosphatase; PINP, propeptide of type-I collagen; CTX, serum | |||
| C-telopeptide crosslinks; PTH, parathyroid hormone; *p=0.04 vs A | |||
Friday, December 15, 2006 7:00 AM
Poster Session II: Treatment: Adjuvant Therapy (7:00 AM-9:00 AM)